The Exposure Signatures Facility Core (ESFC) consists of six analytical resources that contribute unique capabilities to identifying and quantifying toxicants and biological responses to toxicant exposure. High performance omics technologies including epigenomic, transcriptomic, and proteomic analyses are most frequently requested by CURES Center investigators and form the base for the services offered by the ESFC. With Center investigators increasingly focused on questions regarding the interaction of environmental exposure and the physiological response to chemical and non-chemical stressors we have added analytical resources for protein and DNA adducts, small molecule toxicants and metabolites, cellular profiling, cytokines and lipids. Our combined facilities include some of the most advanced analytical capabilities available for targeted and untargeted analysis of the exposome and identification of exposure signatures. Although we focus on the common matrices of blood, plasma and urine, we can work with any biological or environmental sample matrix. Because few investigators are completely familiar with the full scope and power of the services and technologies available through the ESFC, we are available to consult with investigators when they are planning a project. At that time, we offer advice regarding analytical end points they might want to consider, how those end points could be achieved experimentally, and the cost involved in doing that work. Such participation in the design of the project is indispensable, as investigators are rarely familiar with which technology is most appropriate for the study. The ESFC continues to work with investigators once data are obtained. Omics technologies produce data sets that require specialized software available in the laboratory where the data are generated. Using our experience with bioinformatics interpretation of the data sets is the final step offered by the ESFC. The complete ESFC package provides investigators with planning, advanced analytical technology, expert technical assistance and informatics for interpretation of the results.